tbuckley/cabot-search huggingface dataset:
A comparison of the Optum Clinicogenomics Solid Tumor Database and the SEER Population-Based Cancer Registry.
Authors: Alexa Woodward, Pallavi Mohanty, Tze-An Yuan, Yun Liao, Ashley Brenton
Journal: Journal of Clinical Oncology (2023)

6635 Background: Real-world data (RWD) and real-world evidence (RWE) are increasingly utilized across a range of research and regulatory applications, including biomarker discovery, risk stratification, external control arms, and post-market surveillance. Two-thirds of FDA approvals in 2021 utilized genomic data and the growing interest in targeted therapies will likely continue this trend. While genomics or any one type of RWD alone yields an incomplete view of the patient journey, Optum’s clinicogenomic data links de-identified longitudinal clinical and claims data to next-generation sequencing (NGS) results. Ensuring the value of this data requires identifying and limiting biases and maximizing diversity. Methods: To evaluate the robustness and representativeness of Optum’s Clinicogenomic Solid Tumor Database, we compared demographic and clinical characteristics to the Surveillance, Epidemiology and End Results (SEER) database across 16 solid tumor types. Variables of interest included age at diagnosis, sex, self-identified race, year of diagnosis, and metastatic status. The Optum data was derived from clinical data that includes 156 million lives and claims data that covers 95 million lives. The solid tumor sub-cohort used for this analysis included 157,164 patients diagnosed between January 1, 2011, and December 31, 2021 with linked broad-panel NGS results. SEER Incidence Data included patients diagnosed between January 1, 2011, and December 31, 2018. Using the Optum data, we also report average continuous enrollment and sequential testing frequency across all solid tumor types. Results: The overall distributions of age at diagnosis, sex and race were similar across all cancer types, with a few exceptions. On average, SEER had a larger proportions of patients 80 years and older (15% vs 7.2%, all solid tumors) and of Asian race (7.1% vs 3.2%, all solid tumors). Cancer diagnoses in the Optum data increased year over year corresponding with the increasing availability and uptake of genetic testing in oncology, while the SEER data was equally distributed across all years. The average continuous enrollment for solid tumor patients was 8.1 years in the Optum data, and 13% of patients had sequential testing results from &gt;1 time point. Conclusions: Given the increased reliance on RWD and RWE as part of the drug development and regulatory approval processes, ensuring the representativeness of clinicogenomic databases is paramount. This analysis of general patient characteristics across the Optum Clinicogenomics and SEER solid tumor databases found largely similar distributions of key variables. Observed differences between these two representative databases reflect the genetic testing landscape in oncology and provide the opportunity to investigate disparities related to accessing genetic services, corresponding targeted treatment options, and health outcomes.
Comparative analysis between the 8<sup>th</sup> and 7<sup>th</sup> AJCC as a prognostic tool for patients diagnosed with nonmetastatic head and neck soft-tissue sarcoma.
Authors: Angelo Borsarelli Carvalho Brito, Giulia Kodja Zanetta, Felipe D'Almeida Costa, Maria Nirvana da Cruz Formiga, Celso Lopes Mello, Joao Goncalves Filho, Mauro Kazuo Ikeda, Cláudia Malheiros Camillo, Clovis Antonio Lopes Pinto, Victor Hugo Fonseca de Jesus, Fernando Augusto Batista Campos, Luiz Paulo Kowalski, Ulisses Ribaldo Nicolau
Journal: Journal of Clinical Oncology (2023)

e23550 Background: Head and neck soft-tissue sarcoma (HN-STS) is a rare entity for which a new prognostic risk stratification has been proposed in the 8th AJCC. The tumor size 2cm and 4cm have been adopted as cutoffs for T1 to T3 classification and the invasion of surrounding structures denotes T4. In opposite, in the 7th edition the primary tumor size of 5 cm determines T1 and T2 classification. This study aimed to compare the 8th and 7th AJCC as a prognostic tool for HN-STS. Additionally, we sought to investigate prognostic factors in this group of patients. Methods: This is a single Tertiary Hospital study approved by the institutional ethical review committee from the AC Camargo Cancer Center. We retrospectively evaluated patients with non-metastatic HN-STS whose histology subtypes are included in the 40th chapter of the 8th AJCC version. We compared the AJCC 7th and 8th T staging with Cohen’s kappa coefficient using inter-rater agreement analysis. The Kaplan-Meier (KM) estimator was used to calculate median survival times; differences in time-to-event outcomes were assessed using the log-rank test. Cox proportional hazard model was used to assess the effect of features in overall survival (OS). Results: Ninety-five HN-STS treated with curative intent from 2005 from 2021 patients diagnosed were evaluated. Surgical resection (94.7%), radiotherapy (48.4%) and chemotherapy (23.1%) were the employed therapeutic approaches. Leiomyosarcoma and liposarcoma (10 of each subtype) were the most common histology subtypes; High grade disease was present in 66.3%. Kappa coefficient of inter-rater agreement was 0.46 with statistical significance (p = 0.03), which indicates poor agreement between AJCC 7th and 8th T staging system. Regarding OS stratified by T size in the AJCC 7th (T1 and T2) and 8th (T1, T2, T3 and T4) was not statistically different between groups (P = 0.83 and P = 0.21, respectively). Patients with T4 (47.6% vs 78.7%, P = 0.04) and high grade (64.0% vs 96.2%, P = 0.003) had worst 5-years OS. In Cox multivariate analysis, patients with 8th edition T4 and high grade had 3.15- and 4.16-fold increased risk of death, respectively. Conclusions: In our series of patients with HN-STS, neither 7th nor 8th AJCC T size category groups discriminated prognosis. Tumor with local invasion (8th AJCC T4) and high grade were all associated with increased risk of mortality.
Turnaround time of tissue next generation sequencing in cancer patients at a safety net hospital: A quality improvement project.
Authors: Ahan Bhatt, Cristian Papazoglu, Pratibha Shukla, Jennifer J. Wu
Journal: Journal of Clinical Oncology (2023)

e18707 Background: Tissue Next Generation Sequencing (NGS) testing can identify targetable genetic alterations, and has become an essential component of cancer care. Prolonged turnaround time (TAT) for tissue NGS testing (time from ordering until report arrival) can be a barrier for optimal treatment. Reducing the TAT can significantly aid the decision making process and improve the time to treatment initiation. As a quality improvement project, we explored a strategy to improve the TAT at our safety net hospital. Methods: We studied the TAT of commercial NGS test (FoundationOne CDx) ordered between January and December of 2022 by the oncology service at Bellevue Hospital Center (BHC), an affiliated public hospital. Tissue NGS testing was ordered for solid tumors regardless of tumor origin at the discretion of the provider. During the first half of the year, specimens prepared at BHC lab were manually dropped off at a central location for shipping to Foundation Medicine lab (testing site). The workflow was changed on 7/7/2022 to introduce a courier system to pick up the specimens from pathology lab at BHC. We analyzed the data reported by Foundation Medicine. Results: As of 2/1/2023, all specimens ordered between 1/1/2022 to 12/29/2022 were reported. There were 123 reports, of which 122 were used for the analysis. 1 report was excluded due to mislabelling of the specimen at the testing site that led to significant delay in TAT. The mean TAT of all reported specimens for the year 2022 was 23 days. Introduction of the courier reduced the mean TAT from 25 days to 20 days. After introducing the courier system, the mean time for specimen analysis was similar, but the mean time from specimen ordering to arrival at the testing site was reduced from 14 days to 10 days. Conclusions: The TAT for tissue NGS testing in underserved cancer patients at a safety net hospital can be successfully improved by implementing a courier system. The improvement was achieved regardless of tumor origin or patients’ financial ability to pay and can aid decision making for treatment initiation. This strategy can be adopted by community hospitals without access to on-site NGS testing. We are exploring additional interventions to optimize the workflow to further reduce the TAT. [Table: see text]
Comparative analysis of the mutation detection using malignant pleural effusion and blood cell-free DNA samples in lung cancer.
Authors: Yaobin Lin, Sunwen Ji, Yiling Jiang, Tao Wang
Journal: Journal of Clinical Oncology (2023)

e20518 Background: Malignant pleural effusion (MPE) is an abnormal amount of fluid to collect between the chest wall and the lung, and it denotes an advanced malignant disease process. MPE presents a severe medical condition which can result in breathlessness, pain, cachexia and reduced physical activity. MPE is considered to bear cancer signatures because it contains tumor cells released from malignancies, thus can be applied in high-throughput sequencing for cancer screening. Cell-free DNA (cfDNA) in blood consists of small fragments released from apoptotic cells or cancer cells, and pathological conditions can influence this process. Therefore, detection of cfDNA in peripheral blood can identify abnormalities of individuals in a noninvasive manner. Here, we wonder the difference of MPE and cfDNA in lung cancer-related mutation detection. Methods: In this study, MPE and blood samples from 216 patients with late-stage lung cancer were collected and applied to library construction and next-generation sequencing. All samples were collected during August 2018 to December 2022. We focused on the key mutations in cancer-causing genes and drug treatment-related genes (e.g., EGFR, KRAS, BRAF, ERBB2, etc.). Statistical analysis was conducted to compare the detection results between MPE and cfDNA samples by Fisher’s exact test. Results: Among the 216 patients, 60 patients (60/216 = 27.8%) were identified as negative detection with no mutation detected in cancer-causing genes in MPE and blood samples. Of the remaining 156 pairs of samples, there were 118 (118/216 = 54.6%) pairs showing the positive detection in both MPE and blood samples. 12 patients (12/216 = 5.6%) demonstrated the positive detection in blood samples while negative detection in MPE samples. The other 26 patients (26/216 = 12%) demonstrated the positive detection in MPE but negative detection in blood samples. There is no significant difference in detection rates between two types of samples (p = 0.194). Similarity, we next focused on the mutations in drug treatment-related genes and identified 91 patients (91/216 = 42.1%) as negative detection. There were 85 patients (85/216 = 39.4%) showing the same positive detection both in MPE and blood samples. 13 patients (13/216 = 6%) demonstrated the positive detection in blood samples but negative detection in MPE samples. The other 27 patients (27/216 = 12.5%) demonstrated the positive detection in MPE but negative detection in blood samples. No significant difference in detection rates was observed between two types of samples (p = 0.211). Conclusions: The mutation detection results in MPE and blood samples turned out to be consistent in most conditions, suggesting an alternative application of MPE or blood samples in cancer screening. Nonetheless, it is still valuable to integrate the information in both MPE and blood samples for a higher detection sensitivity.
The final analysis of a phase I/II study of nivolumab, ipilimumab combined with nintedanib in advanced non-small cell lung cancer.
Authors: Sonam Puri, Tawee Tanvetyanon, Ben C. Creelan, Michael Rahman Shafique, Andreas Nicholas Saltos, Alberto Chiappori, Eric B. Haura, Ram Thapa, Dung-Tsa Chen, Theresa A. Boyle, Scott Joseph Antonia, Jhanelle Elaine Gray
Journal: Journal of Clinical Oncology (2023)

9102 Background: Nintedanib (NT) is an oral triple kinase inhibitor that is active against NSCLC and inhibits the activity of the immunosuppressive cancer associated fibroblasts in the tumor microenvironment (TME). Targeting the TME with NT may represent an important synergistic approach in improving immunotherapy (IO) outcomes for NSCLC. We initiated a phase Ib/II trial to evaluate the combination of NT, nivolumab (N) and ipilimumab (I) in advanced (a)NSCLC. Based on the phase IB (dose escalation) results, the combination of N (3mg/kg/2w), I (1mg/kg/6w) and NT (150mg once daily) was declared as the recommended phase 2 dose (RP2D). Here we present the final analysis of the regimen in treatment naïve (TN), and IO pretreated (IP) aNSCLC. Methods: This is a single institution, non- randomized, parallel assignment phase I/II clinical trial of aNSCLC pts. Eligible pts were TN (Arm A) or with disease progression following IO (Arm B) with planned sample size of 40/arm. Enrollment into phase II was by the Bayesian two-stage design method with the primary objective of determining the overall response rate (ORR) in the intent to treat population. Key secondary objectives were overall survival (OS) and progression-free survival (PFS). Descriptive statistics were used to summarize demographic and safety data. The Kaplan- Meier method with log-rank test (5% level of significance, 95% CI and 2-sided test) was used for survival analysis. Results: 22 and 29 pts received the N+I+NT at the RP2D in Arm A and B, respectively. The median age was 67 [42;92] with 53% (27/51) females, 84% (42/51) Caucasian, ECOG 1 in 88% (45/51), and a current/prior history of tobacco use in 88% (45/51) pts. Adenocarcinoma histology was common (64%, 33/51) with PD-L1 ≥1% in 52% (22/42) pts. As of Oct 24, 2022, 18 and 26 pts were evaluable for response in Arm A and B, respectively. Clinical efficacy was observed in the TN and IP cohorts (Table). The most common treatment-related adverse events (TRAEs) were similar in both cohorts. TRAE of any grade in Arm A were nausea (8, 36%), diarrhea (8, 36%), fatigue (7, 32%), and in Arm B were nausea (10, 34%), fatigue (9, 31%), anorexia (8,27%). Conclusions: The combination of nivolumab, ipilimumab and nintedanib had a manageable toxicity profile and demonstrated promising antitumor activity in both TN and IP aNSCLC patients. Clinical trial information: NCT03377023 . [Table: see text]
Application of a contralateral esophageal-sparing technique to reduce radiation esophagitis in limited-stage small cell lung cancer treated with twice-daily radiotherapy and concurrent chemotherapy.
Authors: Min Hu, Shuangyan Yang, Yun Chen, Jingjing Kang, Yaping Xu
Journal: Journal of Clinical Oncology (2023)

e20644 Background: Acute esophagitis (AE) is a common radiation-related toxicity after concurrent twice-daily hyperfractionated radiotherapy and chemotherapy in limited-stage small cell lung cancer (LS-SCLC) patients, which could limit dose-escalation of the target and make treatment postponed to decrease local tumor control. More esophageal protective techniques should be proposed to reduce radiation severe esophagitis of LS-SCLC patients. Methods: We retrospectively applied a contralateral esophagus sparing technique (CEST) in 20 unresectable LS-SCLC patients, who had gross tumor within 1 cm of the esophagus and received a total dose of 45 Gy of concurrent twice-daily radiation and standard chemotherapy regimen. The contralateral esophagus (CE) was contoured as an avoidance structure, and the feasibility of CEST on promoting a steep dose falloff beyond the target volume near esophagus was analyzed. The appropriate dose constraints of CE were also investigated. The AE events were recorded according to the RTOG acute toxicity grading system. Results: We performed CEST in 20 LS-SCLC consecutive patients, among whom three patients experienced severe AE after concurrent chemoradiotherapy. Each treatment plan of eligible patients assured high radiation doses delivering, with the planning and gross tumor volume covered by 95% and 100% of the prescription dose. Among these patients, the median maximum esophagus dose declined from 47.9 Gy (range, 46.6-49.7 Gy) to 41.3 Gy (range, 35.9-48.2 Gy), as well as V30 and V36 of esophagus decreased from 9.22 Gy (range, 0.42-17.71 Gy) and 7.39 Gy (range, 0-16.19 Gy) to 2.40 Gy (range, 0-5.68 Gy) and 0.53 Gy (range, 0 -2.69 Gy) after CEST applying, respectively (all p &lt; 0.001). The CE’s median maximum dose, V30, and V36 were 41.3 Gy, 2.13 cc, and 0.24 cc, respectively. Conclusions: By using proposed CE dose constraints of Dmax≤42 Gy, V30 ≤3.5 cc and V36 ≤0.5 cc, we confirmed the feasibility and efficacy of CEST to avoid exposing the esophagus cross-section to high prescription doses in LS-SCLC patients receiving twice-daily hyperfractionated IMRT and concurrent chemotherapy. These findings support the clinical practice of CEST in LS-SCLC patients, while more prospective and large-scale studies are warranted.
Impacts of androgen pathway manipulation on patients with lung cancer.
Authors: Po-Hsin Lee, Jeng-Sen Tseng, Yen-Hsiang Huang, Yu-Wei Hsu, Kuo-Hsuan Hsu, Tsung-Ying Yang, Ho Lin
Journal: Journal of Clinical Oncology (2023)

e21010 Background: Sex hormone may play a role in lung cancer pathophysiology. We aimed to evaluate if androgen pathway manipulation (APM) is associated with better survival in patients with lung cancer, and how finasteride, a 5-alpha reductase inhibitor, impacts androgen receptor (AR) activation and growth of lung cancer cells. Methods: In this retrospective hospital-based cohort study, we screened all men with lung cancer diagnosed during the period from January 2006 to December 2021. APM exposure was defined as using antiandrogens, 5-alpha reductase inhibitors, or gonadotropin-releasing hormone agonists for &gt; 30 days after lung cancer diagnosis. The in vitro study was conducted on A549 lung cancer cells; while the tumor xenograft model was conducted on BALB/c nude mice. Results: Among 4744 men with lung cancer, 98 (2.1%) were identified as having APM exposure. The majority of patients (73.5%) received 5-alpha reductase inhibitors. The patients with APM exposure were older (71.5 vs. 67.0, p &lt; 0.001), had a higher proportion of having prostate cancer (27.6% vs. 1.4%, p &lt; 0.001), and had a smaller proportion of having metastatic lung cancer (41.8% vs. 54.0%, p = 0.003), compared to those without APM exposure. In multivariable Cox proportional hazards analysis, patients with APM exposure experienced better OS compared to those without exposure (Hazard ratio 0.57; 95% CI, 0.44–0.73, p &lt; 0.001). In in vitro study, we illustrated that AR protein stimulated the cell proliferation of A549 cells. Finasteride reduced the AR protein expression and inhibited A549 cell growth. Finasteride promoted ubiquitination and degradation of AR protein and therefore interfered the stability of AR protein. Furthermore, finasteride inhibited cell cycle progression and promoted apoptosis of A549 cells. The in vivo results also supported the inhibition effect of finasteride on lung cancer growth. Conclusions: APM was associated with better OS in male patients with lung cancer. Finasteride interfered with the stability of AR and inhibited A549 lung cancer cell growth. Our findings indicated an oncogenic role of AR on lung cancer which may provide potential therapeutic and targets for lung cancer. The inhibition effect of finasteride on lung cancer might be of benefit for future treatment strategies, prevention and control.[Table: see text]
Predicting non-small cell lung cancer response to immune checkpoint inhibitors with machine learning based on heterogeneous biomarkers.
Authors: Hugo Schmutz, Pierre-Alexandre Mattei, Pierre Tricarico, Sara Contu, Florent Hugonnet, Florian Guisier, Pierre Decazes, David Chardin, Olivier Humbert
Journal: Journal of Clinical Oncology (2023)

e21068 Background: In patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPI), individual clinical, biological, and imaging prognostic biomarkers have recently been identified. However, the combination of these biomarkers has not yet been studied. This study aims to analyse various clinical, biological and 18 FDG PET/CT parameters using machine-learning algorithms to build more accurate prognostic models of NSCLC response to ICPI. Methods: The exploratory cohort consisted of patients with metastatic NSCLC, treated with either pembrolizumab or nivolumab in monotherapy, included in two prospective cohort studies of our institution. For all patients, a total of 28 baseline quantitative features were collected just before the initiation of ICPI (12 clinical, 6 biological and 10 PET/CT parameters), such as the patient’s ECOG performance status, PD-L1 tumour expression level (PD-L1%), neutrophil to lymphocyte blood ratio, number and metabolism of lesions, metabolic tumour volume (MTV). The two endpoints were the progression-free survival at 6 months (6M-PFS) and the overall survival at 12 months (12M-OS). The 28 features were sorted according to their selection frequency by a LASSO logistic regression on extensive cross-validation to predict 6M-PFS and 12M-OS. The top eight features were selected using the intersection of the most frequently selected features of both outcomes and used to build a logistic regression to predict 6M-PFS and 12M-OS. An independent validation cohort was collected to assess the performance of the 8-features model. This cohort consisted of metastatic NSCLC patients treated with monotherapy ICPI and retrospectively included in three different hospitals: Nice (N =16), Monaco (N =10) and Rouen (N =19). We reported the area under the receiver operating characteristic (AUROC). Results: 117 patients were included in the exploratory cohort (N = 93 for training and features selection and N = 24 for the test set). Without any feature selection, the AUROC of the logistic regression was 73.6% and 77.6% on the test set. Using LASSO, the top eight selected features were: age, MTV, number of lesions, PD-L1%, smoking status, ECOG, SUVmax of the most intense lesion and blood sugar level. The AUROC of the 8-features model was 74.3% for 6M-PFS and 85.5% for 12M-OS on the test set. 45 patients were retrospectively included in the validation cohort. The AUROC of the model were 81.9% for the 6M-FPS and 88.2% for the 12M-OS. Conclusions: The combination of heterogeneous biomarkers provides a powerful model for predicting the outcomes of NSCLC patients treated with ICPI. Rigorous feature selection is a critical point in ML approaches to avoid overfitting. [Table: see text]